Describe the double edged sword of drug transportation:

Selective tissue distribution is good.

Toxic accumulation is bad.

What are the 5 overall outcomes of pharmacogenomic differences?

ToxicityProlonged effectUnwanted side effectDrug failure Exploitable feature: some drugs that accumulate in CNS can be used to treat meningitis

23

Describe the pharmacologic basis for ivermectin toxicity in collies

Deletion mutation of mdr1 gene. Dogs that are homozygous for this mutation are affected. With this mutation the transporter does not work and ivermectin accumulates in the brain.

24

How do auto-active receptors present a pharmacologic problem?

Receptor mutation where the receptor is insensitive to the antagonist or inhibitor. The reaction is always going, so the drug or inhibitor have no effect.

25

NEXT STUFF IS DAY'S STUFF

YEEYEE

26

Define concentration-dependence

The % of receptors bound by a drug increases as the concentration of that drug increases

27

Define saturability

This is once all the receptors are bound by a drug, increasing conc of drug will have no effect

28

What is the dissociation constant?

KD = (DxR)/DR; it is the relationship between drug, receptor, and drug-receptor complex

29

Why is the dissociation contstant important?

It describes the drug concentration that is required to produce half the max occupancy of the receptor population

30

Define affinity:

This is chemical attraction

31

What is the equation for affinity?

1/Kd

32

What does a high affinity mean?

This means the drug has a high affinity for the receptor, which means the DR will be high and will be a low dissociation constant

33

What is specificity?

This refers to the selectivity of the drug for a particular receptor

34

What are the three types of modulation of drug binding to receptors and what affect do they have?

1. Competitive inhibition of binding; Will increase the Kd2. Non-competitive inhibition of binding; number of receptors available to be bound are reduced, but the Kd is unaffected3. Allosteric modulation of binding; affinity for the first drug is changed

35

What is an agonist?

Produces the maximum response that can be elicited by those receptors

36

What is a partial agonist?

Produces a response, but is less than max that can be elicited by other agonists at the same receptors

37

What is an antagonist?

Binds to the receptor but does not activate the system. Competitively BLOCKS the activation.

38

Define EC50:

The concentration required of a drug to produce 50% of that drug's max response

39

What is the main measure of a drug's potency? Is a high or low number more potent?

EC50; a low number indicates higher potency

40

What is the difference between Kd and EC50?

Kd: measures affinity EC50: measures potency

41

What is the dose-response relationship?

% of patients that reach a clinically defined response at or below that dose

42

Define ED50:

Dose required to elicit a response in 50% of population

43

Define therapeutic index. Is it better to be high or low?

LD50/ED50; Want a high therapeutic index

44

What is the standard safety margain?

This is the % by which the dose effective in 99% of the population must be increased to cause death in 1% of the population. ((LD1/ED99)-1)x100